Release of neurotransmitters in the spinal cord will be correlated with changes in modulation of activity in nociceptive transmission cells. Microdialysis probes will be placed in the spinal cord dorsal horn of anesthetized cats and monkeys to sample neurotransmitter release. Nociceptive projection cells within the sampling area of the probe will be recorded from extracellularly. Release and modulation will be evoked by electric stimulation of supraspinal sites including nucleus raphe magnus, periaqueductal gray, locus coeruleus, nucleus Kolliker fuse and sensory motor cortex. These sites were chosen for their diverse types of modulatory effects. Glutamate, aspartate, GABA and glycine as well as serotonin and/or norepinephrine will be measured in all dialysis samples using HPLCs with fluorescence and electrochemical detection. Administration of agonists and antagonists through the probes will respectively mimic and block the effects of supraspinal stimulation. Selective spinal lesions will result in loss of specific components of the descending modulation and loss of some neurotransmitter release. These experiments will allow us to match specific neurotransmitters or ratios of neurotransmitters with specific types of modulation of ascending somatosensory information. Taken together, results from these experiments will increase our understanding of sensory processing in the spinal cord and pain processing in particular.